RSV Vaccines

Respiratory syncytial virus (RSV) is a major pathogen in infants, children, and adults. According to the Centers for Disease Control and Prevention (CDC), RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under 1 year of age in the U.S., and is now recognized as a major cause of respiratory illness in adults 65 and older. The global disease burden is estimated at 64 million cases and 160,000 deaths annually. Severe RSV disease results in 3.4 million hospital admissions per year globally with a disproportionate impact on infants less than six months old.

While RSV vaccine development has been underway since the 1950s, there is still no approved RSV prophylactic vaccine on the market. Novavax is leading the development of an RSV vaccine for populations most susceptible to and impacted by the disease that could be administered to children, the elderly, and pregnant women during the third trimester to provide newborns with protection against RSV from the moment of first breath.

Maternal Immunization

The epidemiology of RSV disease suggests that the most severe disease is found in infants (less than 6 months of age). Unfortunately, newborns present challenges to vaccine developers largely due to their immature immune system not responding well to neo-natal vaccines, along with risk factors associated with live RSV infection that include compromised immune systems and elevated susceptibility to disease.

Maternal immunization may therefore be the best way to protect newborns both by the transplacental transfer of protective antibodies and by blocking transmission of the disease. Maternal immunization works through “passive immunity” – the transfer of antibodies from mother to infant in utero providing immunological protection and reduced risk of disease during the first months of life. Maternal immunization is already an important part of the U.S. healthcare system, as data has shown that maternal immunization reduces the disease burden of pertussis and influenza in newborns.

In support of its first clinical trial in pregnant women, scheduled to begin in the fourth quarter of 2014, this May Novavax announced positive Phase 2 interim data from its randomized, blinded, placebo-controlled study of 720 women of childbearing age that demonstrated improved immunogenicity in a one-dose regimen of Novavax’s RSV F-protein vaccine candidate. Kinetic analysis of antibody responses showed rapid increases in antibody levels in all vaccine formulations and dosing regimens. A single 120μg antigen dose generated peak

antibodies within 14 days of immunization with high levels sustained through the 91-day observation period. Such rapid and sustained antibody responses displayed by a single dose of vaccine offers significant flexibility for administration during pregnancy.

The Elderly

In adults, RSV infections (or more accurately, re-infections) are generally mild to moderate in severity, except in people with high-risk conditions including adults with underlying chronic cardiac or pulmonary disease and the elderly. As adults age, their immune systems weaken or are compromised, making them more susceptible to diseases like RSV. It is estimated that between 11,000 and 17,000 adults die of RSV infection annually in the U.S. and up to 180,000 are admitted to hospital with respiratory symptoms.

Novavax recently announced one-year follow-up data on its RSV-F vaccine tested in the elderly in a Phase 1 trial, which demonstrated sustained levels of immune response over a 4 – 6 month period. Because the “RSV season” typically lasts four to five months, these data support further development of this candidate as a seasonal vaccine to protect across a full RSV season, similar to seasonal influenza vaccination.

RSV remains one of the last diseases with a significant global impact but for which a vaccine is not currently available. Novavax is leading the development of an RSV vaccine that has the potential to provide protective immunity to the patient populations most affected by RSV, newborn infants and the elderly.